Homo sapiens Gene: DDX58
Summary
InnateDB Gene IDBG-55854.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol DDX58
Gene Name DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Synonyms RIG-I; RIGI; RLR-1;
Species Homo sapiens
Ensembl Gene ENSG00000107201
Encoded Proteins
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling.
DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade.
DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.
DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well.
DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha.
DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production.
DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecules in antiviral innate immunity.
DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.
DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD).
DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon induction by DDX58.
DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58.
DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice)
Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)
DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.
RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.
ISG15 does not directly alter human rhinovirus replication but modulates immune signalling via the viral sensor protein DDX58 to impact production of CXCL10, which has been linked to innate immunity to viruses.
Human rhinovirus infection of epithelial cells induces the expression and secretion of ISG15, which modulates immune responses via effects on DDX58, and by regulating CXCL10 production.
The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.
Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
DDX58 dually functions as an hepatitis B virus sensor activating innate signalling and as a direct antiviral factor by counteracting the viral polymerase in hepatocytes.
DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.
MIR485 exhibits bispecificity, targeting DDX58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Ddx58 (Rig-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.
[Mus musculus] Ddx58 and Nod2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. Ddx58 negatively regulates ligand-induced NFkB signalling mediated by Nod2, and conversely, Nod2 negatively regulates type I interferon induction by Ddx58. (Demonstrated in human)
[Mus musculus] Ddx58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of Ddx58. (Demonstrated in human)
[Mus musculus] Ddx58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling.
[Mus musculus] Antiviral stress granules containing Ddx58 (RIG-I) and Eif2ak2 (PKR) have a critical role in viral detection and innate immunity.
[Mus musculus] DDX58 (RIG-I) detects cytosolic Listeria monocytogenes infections by sensing secreted bacterial nucleic acids.
[Mus musculus] Ddx58 (RIG-I) is a positive regulator of NF-kB signalling via binding to Nfkb1 mRNA.
[Mus musculus] Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.
[Mus musculus] Ddx58 preferentially binds to coding RNA from S. Typhimurium during infection leading to the expression of IFN beta andthis immunostimulatory activity depends on 5? triphosphorylation of RNA.
[Mus musculus] Ddx58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but Ifih1 is a significant contributor to the cellular defense against IAV.
[Mus musculus] Ddx58 acts in parallel with Zbp1 in an RNA polymerase III-dependent manner to initiate glial responses to herpes simplex virus-1.
[Mus musculus] Mir485 exhibits bispecificity, targeting Ddx58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
Entrez Gene
Summary DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. This gene encodes a protein containing RNA helicase-DEAD box protein motifs and a caspase recruitment domain (CARD). It is involved in viral double-stranded (ds) RNA recognition and the regulation of immune response. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 9:32455705-32526324
Strand Reverse strand
Band p21.1
Transcripts
ENST00000379883 ENSP00000369213
ENST00000379868 ENSP00000369197
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 119 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.
Experimentally validated
Total 119 [view]
Protein-Protein 108 [view]
Protein-DNA 7 [view]
Protein-RNA 2 [view]
DNA-DNA 0
RNA-RNA 1 [view]
DNA-RNA 1 [view]
Predicted by orthology
Total 19 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003725 double-stranded RNA binding
GO:0003727 single-stranded RNA binding
GO:0004386 helicase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0016817 hydrolase activity, acting on acid anhydrides
GO:0042802 identical protein binding
Biological Process
GO:0002230 positive regulation of defense response to virus by host
GO:0008152 metabolic process
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0016032 viral process
GO:0030334 regulation of cell migration
GO:0032480 negative regulation of type I interferon production
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0034344 regulation of type III interferon production
GO:0039528 cytoplasmic pattern recognition receptor signaling pathway in response to virus
GO:0039529 RIG-I signaling pathway
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043330 response to exogenous dsRNA
GO:0045087 innate immune response (InnateDB)
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005923 tight junction
GO:0015629 actin cytoskeleton
GO:0032587 ruffle membrane
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
Antiviral mechanism by IFN-stimulated genes pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated NF-kB activation pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Interferon Signaling pathway
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
Immune System pathway
TRAF3-dependent IRF activation pathway pathway
ISG15 antiviral mechanism pathway
Negative regulators of RIG-I/MDA5 signaling pathway
KEGG
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.190622 Hs.609798
RefSeq NM_014314
HUGO
OMIM
CCDS CCDS6526
HPRD 13131
IMGT
EMBL
GenPept
RNA Seq Atlas